A major challenge for any anatomical study of spatial neglect in neurological patients is that human lesions vary tremendously in extent and location between individuals. Approaches to this problem used in previous studies were to focus on subgroups of patients that are more homogeneous either with respect to the branch territory affected by the stroke or with respect to existing additional neurological symptoms (e.g. additional visual field defects). It could be argued that such strategies might bias the conclusions on the critical substrate associated with spatial neglect. The present study thus addressed the high variability inherent in naturally occurring lesions by using an unselected, but very large sample size and by comparing a neglect group with a non-neglect group using voxelwise statistical testing. We investigated an unselected 7 year sample of 140 consecutively admitted patients with right hemisphere strokes. Seventy-eight had spatial neglect, 62 did not show the disorder. The incidence of visual field defects was comparable in both groups. For assessing lesion location, in a first step, we used conventional lesion density plots together with subtraction analysis. Moreover, due to the large size of the sample voxelwise statistical testing was possible to objectively estimate which brain regions are more frequently compromised in neglect patients relative to patients without neglect. The results demonstrate that the right superior temporal cortex, the insula and subcortically putamen and caudate nucleus are the neural structures damaged significantly more often in patients with spatial neglect.
Various studies have documented that right hemispheric lesions restricted to the basal ganglia or to the thalamus may evoke spatial neglect. However, for methodological reasons, the exact anatomical correlate of spatial neglect within these two subcortical structures still remained uncertain. The present study identified these locations by comparing the anatomy of subcortical lesions to the basal ganglia or thalamus between neglect and control patients. Analysis revealed that the putamen, the pulvinar and, to a smaller degree, the caudate nucleus are the subcortical structures typically associated with spatial neglect in humans. All these structures have direct anatomical connections to the superior temporal gyrus (STG), which recently has been identified as the neural correlate of spatial neglect in the human cortex. Therefore, it is assumed that the right putamen, caudate nucleus, pulvinar and STG form a coherent corticosubcortical anatomical network in the genesis of spatial neglect in humans.
Despite its clinical relevance, direct electrical stimulation (DES) of the human brain is surprisingly poorly understood. Although we understand several aspects of electrical stimulation at the cellular level, surface DES evokes a complex summation effect in a large volume of brain tissue, and the effect is difficult to predict as it depends on many local and remote physiological and morphological factors. The complex stimulation effects are reflected in the heterogeneity of behavioural effects that are induced by DES, which range from evocation to inhibition of responses - sometimes even when DES is applied at the same cortical site. Thus, it is a misconception that DES - in contrast to other neuroscience techniques - allows us to draw unequivocal conclusions about the role of stimulated brain areas.
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